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Defect that causes Huntington's disease has been corrected for the first time (bbc.com)
156 points by tuxguy on Dec 15, 2017 | hide | past | favorite | 40 comments



Since this drug was developed on public funding in the UK, how does that affect its pricing and incorporation in the NHS? I assume whoever gets the license to sell it in the US will have exclusivity and make it expensive as hell.

edit: Never mind, although the research took place at the University of London, it was funded by Ionis Pharmaceuticals (US) and further by Roche (Swiss multinational). The Guardian article relegates that bit of info to the very last line, as if they were just a minor part of the effort. http://markets.businessinsider.com/news/stocks/Ionis-Pharmac...


Great news. Although it's already too late for my mother, my sister can definitely profit from it if it turns out well. And I guess I will have to take the test now to see whether I have the disease as well...


Best of luck.


Slightly off-topic, but there is an interesting connection between Chorea Huntington and the evolution of complex brains and intelligence:

https://www.economist.com/news/science-and-technology/216457...


Interesting connection with brain complexity, but note that the function of the Huntinton's gene remains poorly understood.

Something that may be related... The same unstable repeat that causes the disease is ancient and is conserved throughout mammals! So other mammals can get a similar disease driven by the same mutations. This is useful for generating models of the disease in other mammals (e.g. mice). Such conservation of repeats is exceptionally rare.


"Corrected" seems a bit strong. The treatment mitigates the cause of the disease but it's not a cure, at least not yet. Does sound promising.


This is awesome. Unfortunately, we lost both my cousin and uncle from this but I'm glad I'm finally seeing a potential cure for this horrible disease.


If anyone has a bit of spare time, The Inheritance is a documentary worth watching. It’s about a family with Huntington’s disease and them living and dying with it. No affiliation.

https://theinheritancedocumentary.com


I wonder if this can be extended to other brain related illnesses such as Alzheimers.


I think the treatment will generalise better to other genetic diseases than to other brain diseases, let alone a brain disease like Alzheimer for which the cause is badly understood.



Really cool to see progress on this terrible disease.


TL;DR

Huntington's is caused by an error in a section of DNA called the huntingtin gene. Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development. But a genetic error corrupts the protein and turns it into a killer of brain cells. The treatment is designed to silence the gene.

One fear was the injections could have caused fatal meningitis. But the first in-human trial showed the drug was safe, well tolerated by patients and crucially reduced the levels of huntingtin in the brain.

The UCL scientist, who was not involved in the research, says the same approach might be possible in other neurodegenerative diseases that feature the build-up of toxic proteins in the brain. The protein synuclein is implicated in Parkinson's while amyloid and tau seem to have a role in dementias. Off the back of this research, trials are planned using gene-silencing to lower the levels of tau.


I wish all articles were written like your tldr. The BBC article is atrocious, it reads like a list of bullet points. A single sentence per paragraph, no flow.


They're going after the Daily Mail readers who can cope with a few more syllables in their words.


Here is the Guardian piece on it that reads much better. https://www.theguardian.com/science/2017/dec/11/excitement-a...


I wonder how this genetic error could propagate wide enough for the disease to get a name.

It's clearly maladaptive, isn't it?

Of course, same question could be asked for BRCA.


There is something important about the type of mutations that drive Huntington's.

Huntington's is caused by an expanded repeat composed of (CAG)n with n>40 repeats. Due to the instability of repeat regions, new mutations arise in this gene at a relatively high rate. So, even if there were strong selection against expanded repeats the disease would continue to exist. However, as mentioned by others here, strong selection is unlikely due to the late age of onset of the disease. So mutation continues to introduce the disease and selection has been too weak to remove it.

In contrast, BRCA mutations differ from the Huntington mutations. BRCA mutations are single "point" changes in the sequence, known as SNPs, that disrupt the protein function. Novel point mutations are exceptionally rare.

So, unlike with BRCA, when investigating why Huntinton's disease exists, one must consider BOTH mutation and selection.


Huntington's also has an interesting place in the history of genetics, genetic diseases, and heredity.

I wish I could find the excerpt, but the book The Gene talks about the original research and it's an interesting story.

The book is worth reading in general (Siddhartha Mukherjee is a great writer and it's really good).

http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mu...


Because it usually only kicks in after childbearing years, until relatively recently there's not been a test for it, so no way to know if you'd pass it onto your children, and in the last 200 years life expectancy has gone past the age at which is kicks in, highlighting it more.


> Because it usually only kicks in after childbearing years

Orphans are not a very good evolutionary tactics. But you definitely have a point otherwise. Had it earlier onset age, it would have no way to propagate.


Historically 30-50 would be often be grandparents or great grandparents which has much less evolutionary pressure. Though they would likely still have underage kids.


Historically those kids would have been working already.


A 50 year old can have great grand kids, and a 3 year old at the same time. Though with a large extended family someone can also probably take over in the case something happens.


Do you still call them "orphans" if they're in their mid to late 20s?


See my other comment for a possible explanation. There seems to be a link between complex brain development and Chorea Huntington, where a higher number of triplets in the gene leads to higher intelligence or more complex brains, but when the number gets too high the disease develops.


I don't think it's clearly maladaptive. We age and die because it's adaptive to do so. It's possible we've retained a predilection for developing huntington's because it's energy efficient to have some grandparents die.

I'm not arguing that this is necessarily the case, but it is not clearly maladaptive.


What the BBC doesn't say is that this is an important step towards eventually being able to genetically modify healthy, adult people.

It's a trojan horse, and the clever thing about it is that there are valid medical reasons for it.


The described treatment degrades mRNA; no genetic modifications are made.


I stand corrected.

I can't edit or remove my comment because Hacker News believes they know better than me if I should have the ability to edit or remove my own comments.



Why is this an important step towards eventually being able to genetically modify healthy, adult people?


And why is it wrong for healthy people to have modifications done?


Because it could be forced on them.


Well, sure, that's possible. But then it would be the forcing that's wrong.


In my view, having the tech is what's wrong, because then it will be inevitably misused by the ruling classes to potentially catastrophic effect.

You effectively can't trust the regulators of something so potentially disruptive of the balance of power.


Yes, plastic surgery for example


What is wrong with people having plastic surgery exactly?


Ushering the age of the super humans


Super servants.

In Blade Runner, Replicants were not robots. They were genetically modified human beings designed to make them perfect slaves.

I don't expect perfection, but I expect an attempt at forcibly modifying people to make them healthier and satisfied in an increasingly unhealthier society.

No need to reform society if you can change human nature.




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